EP 2825535 B1 20160427 - A METHOD OF PREPARING THE SCOPINE ESTER OF DI-(2-THIENYL)GLYCOLIC ACID, AN INTERMEDIATE IN THE SYNTHESIS OF TIOTROPIUM BROMIDE, AND ITS NEW FORM
Title (en)
A METHOD OF PREPARING THE SCOPINE ESTER OF DI-(2-THIENYL)GLYCOLIC ACID, AN INTERMEDIATE IN THE SYNTHESIS OF TIOTROPIUM BROMIDE, AND ITS NEW FORM
Title (de)
VERFAHREN ZUR VORBEREITUNG DER SCOPINESTER VON DI-(2-THIENYL) GLYKOLSÄURE, EIN ZWISCHENPRODUKT IN DER SYNTHESE VON TIOTROPIUMBROMID UND SEINE NEUE FORM
Title (fr)
PROCÉDÉ DE PRÉPARATION DE L'ESTER DE SCOPINE DE L'ACIDE DI-(2- THIÉNYL)GLYCOLIQUE, UN INTERMÉDIAIRE DANS LA SYNTHÈSE DU BROMURE DE TIOTROPIUM, ET SA NOUVELLE FORME
Publication
Application
Priority
- CZ 2012190 A 20120316
- CZ 2013000041 W 20130314
Abstract (en)
[origin: WO2013135219A1] The invention relates to a preparation method of the scopine ester of di-(2- thienyl)glycolic acid of formula I. The scopine ester of formula I is an important intermediate in the synthesis of tiotropium bromide, the substance with the chemical name (1R,2R,4S,5S,7S)-7-(2-hydroxy-2,2-di(thiophen-2-yl)acetoxy)-9,9-dimethyl-3- oxa-9-azatricyclo[3.3.1.02'4]nonan-9-ium bromide of formula II. The method consists of the following steps, reaction of scopine of formula III with derivatives of oxalic acid of formula XIII, wherein X means F, CI, Br, I, and R is X or O-terf-butyl, O-methyl, A/-pyrrolidinyl, N-morpholinyl and /V-imidazolyl, in the presence of a weak base and a catalyst in an inert organic solvent, producing the derivative of formula XIV; reaction of the derivative of formula XIV with at least 2 equivalents of 2- thienylmagnesium bromide of formula XV; and isolating the resulting scopine ester of formula I is then and crystallization from a crystallization solvent.
IPC 8 full level
C07D 451/10 (2006.01)
CPC (source: EP)
A61P 11/00 (2017.12); A61P 11/06 (2017.12); A61P 11/08 (2017.12); C07D 451/00 (2013.01); C07D 451/10 (2013.01)
Designated contracting state (EPC)
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
Designated extension state (EPC)
BA ME
DOCDB simple family (publication)
WO 2013135219 A1 20130919; CO 7071141 A2 20140930; CZ 2012190 A3 20130925; CZ 304808 B6 20141105; EP 2825535 A1 20150121; EP 2825535 B1 20160427; ES 2581534 T3 20160906; HU E029555 T2 20170328; PT 2825535 T 20160714
DOCDB simple family (application)
CZ 2013000041 W 20130314; CO 14196751 A 20140905; CZ 2012190 A 20120316; EP 13716178 A 20130314; ES 13716178 T 20130314; HU E13716178 A 20130314; PT 13716178 T 20130314